In the opening shot, we see Jim and Michelle's (Jason Biggs and Alyson Hannigan) bedroom with clothes lying around everywhere while R. Kelly's "Bump n Grind" plays. The bed is rocking, but it turns out to be Michelle bouncing to get their two-year-old son, Evan, to fall asleep. When he does, she takes him to his room and tells Jim she's gonna take a bath. When she's gone, Jim grabs a tube sock, fills it with lube, and starts whacking it to porn on his laptop computer, until Evan suddenly is standing before him. As Jim frantically tries to close the porn, he ends up slamming the laptop shut on his penis and throws the sock on Evan's head. The boy points out that Jim's bleeding so Jim goes to the bathroom to find medicine, only to walk in on Michelle also in the bathtub masturbating with the shower head. Both of them are embarrassed.
The next day, Jim, working in a office cubicle, calls up Kevin Myers (Thomas Ian Nicholas), who's working in the kitchen, but has a home job as an architect. He overhears his overbearing wife, Ellie, come in reminding Kevin to watch "Real Housewives" with her. He asks Jim if he's going to the reunion. It'd be the four of them (along with Oz and Finch) and no Stifler. Jim asks if Oz would be down with it considering his job, and nobody knows where Finch is.
Meanwhile, Oz (Chris Klein) is a sportscaster interviewing Chad Ochocinco. The interview plays on TV while Oz comes home and finds his hot new girlfriend Mia (Katrina Bowden) in the jacuzzi with another man who turns out to be gay. Oz also considers going to the reunion while Mia is on the phone arguing with her friend Rumer Willis.
Elsewhere, the crafty and misanthropic Stifler (Seann William Scott) is seen going around a workplace hitting on women and mocking his co-workers and strolling into an office, rubbing a pic of a hot blonde on his junk before his actual mean-spirited boss, Mr. Duraiswamy, comes in and reveals Stifler is just a temp. He berates him and tells him to get back to work.
Jim and Michelle drive to Noah's -Jim's Dad- (Eugene Levy) house trying to forget what Evan saw. Once there, Jim runs into his old neighbor Kara (Ali Cobrin), the girl he used to babysit whom is now a 17-going-on-18-year-old teen. She's way hot and runs up to Jim, who doesn't immediately recognize her. She invites him to her birthday party while her douchebag boyfriend hurries her up.
Jim goes to his old bedroom where he starts remembering his webcam incident with Nadia from the first movie, and then sees the porn mags his dad got him. That's when Noah ends up walking in and telling Jim how now that he has a kid, Jim will someday tell him all about the same sexual things his dad told him. Jim asks Noah if he had gotten back out there with dating since his wife/Jim's mom passed away three years ago, but he hasn't.
Jim meets up with Kevin and Oz before Paul Finch (Eddie Kaye Thomas) comes in on a motorcycle looking all badass. They go into the Jilly's Bar where Finch tells them about his travels of the world and joining an African tribe and having the burn-mark to prove it. They are recognized by the bartender Selena (Dania Ramirez), who used to be a dorky fat band geek and old friend of Michelle. The guys look at their yearbook and read their wish list. Oz hoped to coach his son's lacrosse team. Finch hoped to find true love, Kevin hoped to stay with Vicky, and Jim wanted to have Ricky Martin's sex life (until now, of course). Stifler then pops in and buys them all a round of shots. This leads to Jim waking up in his kitchen the next morning, pants-less, and getting caught by Michelle and Selena.
Everybody goes to the beach later that day. Oz finds his old girlfriend Heather (Mena Suvari), who is dating a man named Dr. Ron (Jay Harrington), a cardiologist the hospital where she currently works as an intern. Suddenly, AJ, Kara's douche boyfriend, steals Mia's bra top, as well as a few other girls', and sprays the guys with his jet ski. The gang plots some payback, which Stifler says would just be them stealing their beer, when he, in fact, ties their jet skis up and takes a shit in their cooler. AJ unwittingly sticks his hand in the shit and witnesses Stifler driving away and dragging the jet skis out of the water and into some trees.
After this, the guys meet up with Vicky (Tara Reid), Kevin's former girlfriend. Later that evening, they go by the lake and walk into Kara's birthday party. She starts flirting with Jim and Stifler encourages him to bang her. Meanwhile, Oz, Heather, Mia, and Ron play a drinking game which gets awkward when Mia calls Heather a prude and when Ron privately asks Oz if he wouldn't mind trading girlfriends. Elsewhere, Finch continues telling Selena about his traveling adventures and they make out. Also, Kevin does some catching up with Vicky, who tells him she dumped her last boyfriend.
Jim takes a drunk Kara home, who tells Jim she wants him to be her first. She takes her top off and tries to takes his pants off, but he swerves off the road and she bumps her head against the steering wheel, knocking herself out. A car comes up, and it turns out to be one of the MILF guys, telling Jim he's in charge of the reunion. When he leaves, he calls the guys for help, and they decide to create a distraction so he can get Kara inside her house without her parents knowing she was drunk.
Oz, Finch, and Stifler are invited into the house by Kara's parents when her mom recognizes Oz from "Celebrity Dance-Off" (which is evidently, all Oz is remembered or known for). She hits on him as Jim and Stifler sneak the nude Kara upstairs, put clothes on her and manage to get out undetected. When Jim gets home, Michelle has prepared a sexy night for him, but he's already passed out. Meanwhile, Kevin wakes up to Vicky blowing him. Turns out that was just a dream, but he really was sleeping next to her. He leaves in a panic.
The next evening, Jim and Michelle agree to spice up their sex life at Stifler's party, and they give Noah a makeover so he can join them. At the party, Stifler is pissed off to see how lame the party is going. Two of his former lacrosse buddies announce their engagement (apparently half the lacrosse team was gay). Mia takes ecstasy while Oz refuses. Kevin confronts Vicky about the night before, but she tells him that their clothes were off because he fell in the lake while drunk. He is relieved that he didn't have sex with her, but she leaves upset that he thought of her like that. Stifler meets a girl who used to blow him, Loni, only to see that she got fat. Desperate, he takes her to the bathroom where she makes him go down on her. A few minutes later, Ron arrives at the party with Heather bringing a DVD of Oz on Celebrity Dance-Off, hosted by Neil Patrick Harris. Oz loses to Gilbert Gottfried and further embarrasses himself by making an impassioned speech about dancing. Later, he goes to the basement and is met by Heather, and he admits he regretted losing her. He kisses her, but after she leaves, Mia straddles him, and the two girls fight, with Heather ripping off one of Mia's extensions.
Meanwhile, Noah meets Stifler's Mom (Jennifer Coolidge). The two get drunk and stoned talking about their sons. At the Levinson house, Jim and Michelle try having sex in dominatrix outfits, but Kara comes in trying to seduce him again. That's when AJ comes in after following her and tries to beat Jim up. This leads to a huge fight outside, which is broken up by the cops whom arrest both Jim and AJ. They arrest Finch after they reveal that the motorcycle that he rode in on had been reported stolen (Finch apparent stole the motorcycle to impress his friends). Jim is forced to confront Michelle about Kara trying to seduce him, which upsets both girls.
The next morning, Michelle has gone to stay with her grandmother, so Jim talks to his father about his lack of a sex life. Jim's Dad tells him that they need to make time for each other while managing their son, as he and his wife did when Jim was a boy (explaining why he went to Hebrew school so much).
On the night of the reunion, and the boys gather once again, after Finch's mom bails him out of jail. He reveals he stole the motorcycle from his boss after he didn't give him a raise and that he actually works as an assistant manager at Staples. Oz says Mia broke up with him and left. They look at the senior wish list on the wall of the high school and see Stifler's quote of "hoping to keep the party going with his boys." They find him at work, and they all encourage him to come with them before the asshole boss comes in. Stifler finally stands up for himself and completely browbeats the scumbag boss in front of his girlfriend.
At the reunion, Kevin meets Jessica (Natasha Lyonne) who reveals that she recently came out as a lesbian and has brought her butch girlfriend as her date. Jessica tells Kevin to talk to Vicky, where they make amends after he realizes that while he is happily married, he never forgot Vicky as being his first love. Ellie comes in, meets Vicky, and invites her to dance with both of them. Finch hooks up with Selena again since she didn't care about his cool stories, just that he was the nice guy who noticed her before. Oz and Heather kiss, which provokes Ron, who makes fun of Oz, who moves into hit Ron for the insult. Ron yells at Oz that if he punches him, he'll sue Oz for all he's worth. Stifler responds by punching Ron out, since he "ain't worth jack shit." Stifler also helps Sherman, aka "The Sherminator" hook up with Loni after he sadly reveals he is divorced with custody of his kid Furlong (yes, after Edward Furlong). Jim and Michelle have sex in the band classroom, where they are spotted by Nadia (Shannon Elizabeth) and her short dorky boyfriend. She compliments Jim on being better at containing his excitement. Finally, Stifler is asked by the gay teammates to plan their wedding, which he accepts, and then meets Finch's mom, who is also smoking hot, and the two have sex on the lacrosse field. They are watched by the MILF guy, who reunites with his MILF buddy, and they chant "MILF!" as they watch Stifler bone Finch's mom.
The next day, the boys talk about how much fun they had. Jim sees Kara, and the two reconcile over their behavior. The guys sit at their favorite restaurant, where Oz reveals he is staying in town with Heather, and Finch and Selena are planning to go to Europe. They all agree to meet up once a year. As the movie closes, Stifler mumbles that he banged Finch's mom.
During the end credits, we see Noah and Stifler's Mom at the movies. He puts his arm around her, and she responds by blowing him as he excitedly exclaims loud enough for the audience to hear. As he finishes, he looks at the people next to him and replies: "Great movie."